Emergency Department and Intensive Care Unit, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
Department of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
Oxid Med Cell Longev. 2022 May 24;2022:2657713. doi: 10.1155/2022/2657713. eCollection 2022.
Sepsis-associated encephalopathy is a common neurological complication of sepsis. Despite advances in pathological and diagnostic investigations, its treatment remains a major challenge. In sepsis-associated encephalopathy, neuroinflammatory overactivation and mitochondrial damage are thought to contribute to cognitive and behavioral impairments. In this study, we found that administration of (-)-Epicatechin, a dietary flavonoid of the flavan-3-ol subgroup, improves memory deficits and behavior performance by ameliorating neuroinflammation, regulating mitochondria function, enhancing synaptic plasticity, and reducing neuronal loss in a mouse model of lipopolysaccharide-induced sepsis. We further show that the AMPK signaling pathway might be among the mechanisms involved in the beneficial memory effects. Our data demonstrated the potential of (-)-Epicatechin as a new drug candidate for the treatment of sepsis-associated cognitive impairment by targeting AMPK.
脓毒症相关性脑病是脓毒症的一种常见神经系统并发症。尽管在病理和诊断研究方面取得了进展，但该病的治疗仍然是一个主要挑战。在脓毒症相关性脑病中，神经炎症过度激活和线粒体损伤被认为导致认知和行为障碍。在这项研究中，我们发现膳食黄烷醇类黄酮的 (-)-表儿茶素可通过改善神经炎症、调节线粒体功能、增强突触可塑性和减少脂多糖诱导的脓毒症小鼠模型中的神经元丢失来改善记忆缺陷和行为表现。我们进一步表明，AMPK 信号通路可能是参与有益记忆作用的机制之一。我们的数据表明，(-)-表儿茶素可能是一种通过靶向 AMPK 治疗脓毒症相关性认知障碍的新药候选物。
